SEARCH · PubMed Health

Results for “modularity”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 379 records · Page 21Linked to original sources

PubMed1999

Association of neuronal calcium channels with modular adaptor proteins.

Presynaptic voltage-gated calcium (Ca(2+)) channels mediate Ca(2+) influx into the presynaptic terminal that triggers synaptic vesicle fusion and neurotransmitter release. The immediate proximity of Ca(2+) channels to the synaptic vesicle release apparatus is critical for rapid and efficient synaptic transmission. In a series of biochemical experiments, we demonstrate a specific association of the cytosolic carboxyl terminus of the N-type Ca(2+) channel pore-forming alpha(1B) subunit with the modular adaptor proteins Mint1 and CASK. The carboxyl termini of alpha(1B) bind to the first PDZ domain of Mint1 (Mint1-1). The proline-rich region present in the carboxyl termini of alpha(1B) binds to the SH3 domain of CASK. Mint1-1 is specific for the E/D-X-W-C/S-COOH consensus, which defines a novel class of PDZ domains (class III). The Mint1-1 PDZ domain-binding motif is present only in the "long" carboxyl-terminal splice variants of N-type (alpha(1B)) and P/Q-type (alpha(1A)) Ca(2+) channels, but not in R-type (alpha(1E)) or L-type (alpha(1C)) Ca(2+) channels. Our results directly link presynaptic Ca(2+) channels to a macromolecular complex formed by modular adaptor proteins at synaptic junction and advance our understanding of coupling between cell adhesion and synaptic vesicle exocytosis.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Modular structure of a docking surface on MAPK phosphatases.

Mitogen-activated protein kinases (MAPKs) must be precisely inactivated to achieve proper functions in the cells. Ten members of dual specificity phosphatases specifically acting on MAPKs, termed MAPK phosphatases (MKPs), have been reported. Each member has its own substrate specificity that should be tightly regulated. However, the molecular mechanism underlying the regulation of the specificity is largely unknown. In the MAPK signaling pathways, docking interactions, which are different from transient enzyme-substrate interaction, are known to regulate the enzymatic specificity. Here we have identified and characterized a docking surface of MKPs. Our results show that a docking surface is composed of a tandem alignment of three subregions (modules): a cluster of positively charged amino acids, a cluster of hydrophobic amino acids, and a cluster of positively charged amino acids (positive-hydrophobic-positive). This modular structure well fits the docking groove on MAPKs that we have previously identified and may contribute to regulating the docking specificity of the MKP family. The position, number, and species of charged amino acids in each module including the central hydrophobic subregion are important factors in regulation of docking to specific MAPKs. This modular structure in the docking interaction may define a novel model of protein-protein interaction that would also regulate other systems.

Amino Acid Sequence↗

PubMed2002

Modular arrangement and secretion of a multidomain serine protease. Evidence for involvement of proline-rich region and N-glycans in the secretion pathway.

The Limulus Factor C (FC), a multidomain glycoprotein that binds bacterial endotoxin with high affinity, belongs to the serine protease family of the complement and blood coagulation cascade. Here, we provide compelling evidence for the importance of modular arrangement and relevance of the proline-rich region (PRR) and N-glycosylation to the secretion and function of FC. We propose that PRR could be a universal conformational domain that regulates protein folding and targeting. FCs lacking PRR preceding the serine protease domain, were localized intracellularly. Misfolded conformers of the intracellular FCs were more susceptible to trypsin digestion. Glycosylation inhibition studies indicate that the presence but not the exact structure of the N-glycans affects the secretion of FC, although the complexity of glycosylation may influence its endotoxin-induced proteolytic cleavage with resultant enzymatic activity. Disruption of specific N-glycan sites at positions 740, 767, and 912, downstream of the PRR, at or near the serine protease domain, blocks its secretion. Co-expressed molecular chaperones like canine calnexin associates with glycosylated FCs to increase its solubility and secretion level but did not alter their expression profiles. Our results clearly demonstrate that the folding and secretion of a multidomain serine protease like FC are determined by its modular domain arrangement and site-specific N-glycans. The secreted FCs containing the N-terminal portion of FC are able to detect lipopolysaccharide with high sensitivity. We also identified the lectin-like and sushi 4 domains to contribute to the binding of lipopolysaccharide.

Amino Acid Sequence↗

PubMed2002

Variation, plasticity and modularity in anuran development.

Although anuran development is generally thought to be relatively conservative, a great deal of variation is evident when different species are compared. This report summarizes the results of comparative analyses of different aspects of anuran development. These include differences in sequence and timing of developmental events, the effects of genome size, and the effects of different life history strategies on anuran embryogenesis. The results show that anuran development is plastic at the evolutionary level, and many changes can occur in the developmental processes of anurans throughout their evolution. Changes are apparently rapid, and are as common as cladogenic events. This evolutionary plasticity can be attributed to the modular nature of anuran development. Different modules can shift relative to one another in time or in space, creating variations in the observed developmental patterns. However, shifts in modules can occur even without having a significant effect on the ultimate outcome of the process. I discuss the implications of the modular nature of development on the evolution of anuran development, and of the group in general.

Journal Article↗

PubMed1991

Neuroscience, modularity and personality theory: conceptual foundations of a model of complex human functioning.

The purpose of this paper is to lay the groundwork for the development of a scientific theory of complex human functioning. We first discuss the assumptions on which our thinking is based, then advance the argument that behavior, and human activity in general, may be more fully understood in light of current data on the structural organization of the central nervous system. The brain is organized as a modular, distributed, self-organizing system, which is in constant transaction with the environment. Because of its plasticity, structural and functional change occurs in the brain as a result of experience throughout life. It is our thesis that complex human behavior is organized in a similar manner - that is, human personality and behavior manifest themselves as modular systems. The insights provided by an understanding of the relationship of brain and behavior may enhance the capacity to explain both normal and pathological personality functioning.

Adaptation, Psychological↗

PubMed2004

The Yorkshire Modular Training Programme: a model for structured training and quality assurance in obstetrics and gynaecology.

Recent changes in postgraduate education have highlighted the need for structured training to ensure quality in training and optimize patient care. In Yorkshire, a "modular" approach to postgraduate education in obstetrics and gynaecology has been adopted through the Yorkshire Modular Training Programme (YMTP). The curriculum for trainees is divided into "modules" organized over five years. This provides a comprehensive educational package covering all aspects of obstetrics and gynaecology for trainees in the specialty. The YMTP provides a framework for region-wide integration and ownership of responsibility for teaching and training. It also provides quality assurance in education throughout the region and provides an "educational continuum" in which the different modules work together to meet the educational requirements of the trainees. It also aims to integrate "training" and "education" for the trainees. This paper describes the organization of the programme including its educational principles. It discusses its strengths and weaknesses. It provides a useful framework for postgraduate education that could be used by other regions.

Curriculum↗

PubMed1995

On the modularity of face recognition: the riddle of domain specificity.

The present paper focuses on the modular attributes of face recognition, defined in terms of domain specificity. Domain specificity is examined by looking into the innate nature of face recognition, the special effects related to the recognition of inverted faces, the specificity of electrophysiological responsivity to facial stimuli, and the specific impairment in face recognition associated with localized brain damage. Converging evidence from these sources seems to consistently show that face recognition is not qualitatively unique, as it proceeds in a manner similar to the recognition of other visuospatial objects. However, it seems to be special in that it may involve specific mechanisms dedicated to face recognition. Among infants, differential responsivity to faces and to other objects in terms of age of onset, attraction and course of development, seems to indicate the operation of a special process. Unusual inversion effects in face recognition might be due to the special expertise that humans develop for recognizing upright faces. Face-selective single unit responses in the monkey's brain implies the existence in the visual system of cells which are exclusively dedicated to the processing of facial stimuli. Finally, in prosopagnosia localized brain damage is linked to a specific inability to recognize familiar faces. Taken together, the data seem to show that some elements in the process of face recognition are domain specific, and in that sense, modular.

Agnosia↗

PubMed2004

Total modular wrist prosthesis: a new design.

The common modes of failure of total wrist arthroplasty have been fracturing, loosening, pain on pronation and supination, and muscle soft-tissue imbalance. To overcome some of these problems a total modular wrist prosthesis has been designed for use both as a primary prosthesis and for revision surgery. An uncemented and cemented radial component, secure fixation in three metacarpal bones, and an unconstrained and constrained version account for the modularity, including optional treatment of the distal radioulnar joint. We present the design of the prosthesis including the preliminary clinical and radiographic results after a mean follow-up of 20 months in 32 patients of whom four have had earlier implants revised.

Adult↗

PubMed2006

Treatment of ballast water; how to test a system with a modular concept?

A variety of methods were successfully applied to examine the efficacy of a modular ballast water system according to the standards as adopted by the International Maritime Organization. The ballast water treatment system had a capacity of 530 m3 h(-1) consisted of a pump system, a hydrocyclone, a 50 microm mesh-size self-cleaning filter and an installation for the addition of a chemical disinfectant (PERACLEAN Ocean). The land-based testing facility used natural sea water of high turbidity during the spring phytoplankton bloom. The mesozooplankton fraction was inspected with a standard binocular. Larger zooplankton were effectively removed with the filter; the smaller sized fraction containing larvae and nauplia were killed after chemical treatment. The phytoplankton component was monitored using flow cytometry. The huge colonies of the phytoplankton Phaeocystis globosa were disrupted in the hydrocyclone liberating the colony cells which passed as single cells through the filter. These cells remained viable but were finally killed in the secondary (chemical) step. Bacteria also passed all mechanical treatment steps unharmed but were killed in the final step. Viability tests with SYTOX Green, which were specifically designed for phytoplankton, showed that mechanical treatment did not affect the percentage of viable cells a short-term, but after several hours the viable cell counts dropped down to 70%. Phytoplankton cells recovered within a single day and formed a new dense bloom rapidly. The bacteriostatic component of the chemical disinfectant (H2O2) remained present for several days preventing regrowth of bacteria for up to 15 days after addition. In conclusion, the IMO standards were met using the modular ballast water treatment unit and the applied instruments and assays were effective and rapid tools to qualify and quantify the organisms present as well as their viability.

Animals↗

PubMed2003

Modular representation of the guideline text: an approach for maintaining and updating the content of medical education.

One of the principal challenges in the medical practice is the update of their knowledge. One of the prime roles of the Continuing Medical Education is to train the medical practitioners with the latest advances in health care, specialized to their needs. Online courses and classroom teaching with computer-based representations have become an established mode of delivering medical education. This paper deals with the modularized representation of a medical text concerning clinical practice guidelines. The proposed system takes into consideration the semantics of the Unified Medical Language System and is based upon the marking up and display of the knowledge using the XML and XSLT languages. This modularization of the concepts leads to the determination of the context of a portion or the whole document. Thus, after marking up using our system, the text components can be exchanged, modified or reconstructed, which, in turn, would help to maintain the updates in medical knowledge.

Artificial Intelligence↗

PubMed1997

Role of the modular domains of SR proteins in subnuclear localization and alternative splicing specificity.

SR proteins are required for constitutive pre-mRNA splicing and also regulate alternative splice site selection in a concentration-dependent manner. They have a modular structure that consists of one or two RNA-recognition motifs (RRMs) and a COOH-terminal arginine/serine-rich domain (RS domain). We have analyzed the role of the individual domains of these closely related proteins in cellular distribution, subnuclear localization, and regulation of alternative splicing in vivo. We observed striking differences in the localization signals present in several human SR proteins. In contrast to earlier studies of RS domains in the Drosophila suppressor-of-white-apricot (SWAP) and Transformer (Tra) alternative splicing factors, we found that the RS domain of SF2/ASF is neither necessary nor sufficient for targeting to the nuclear speckles. Although this RS domain is a nuclear localization signal, subnuclear targeting to the speckles requires at least two of the three constituent domains of SF2/ASF, which contain additive and redundant signals. In contrast, in two SR proteins that have a single RRM (SC35 and SRp20), the RS domain is both necessary and sufficient as a targeting signal to the speckles. We also show that RRM2 of SF2/ASF plays an important role in alternative splicing specificity: deletion of this domain results in a protein that, although active in alternative splicing, has altered specificity in 5' splice site selection. These results demonstrate the modularity of SR proteins and the importance of individual domains for their cellular localization and alternative splicing function in vivo.

Alternative Splicing↗

PubMed2004

Branching and self-organization in marine modular colonial organisms: a model.

Despite the universality of branching patterns in marine modular colonial organisms, there is neither a clear explanation about the growth of their branching forms nor an understanding of how these organisms conserve their shape during development. This study develops a model of branching and colony growth using parameters and variables related to actual modular structures (e.g., branches) in Caribbean gorgonian corals (Cnidaria). Gorgonians exhibiting treelike networks branch subapically, creating hierarchical mother-daughter relationships among branches. We modeled both the intrinsic subapical branching along with an ecological-physiological limit to growth or maximum number of mother branches (k). Shape is preserved by maintaining a constant ratio (c) between the total number of branches and the mother branches. The size frequency distribution of mother branches follows a scaling power law suggesting self-organized criticality. Differences in branching among species with the same k values are determined by r (branching rate) and c. Species with r< r/2 or c>r>0). Ecological/physiological constraints limit growth without altering colony form or the interaction between r and c. The model described the branching dynamics giving the form to colonies and how colony growth declines over time without altering the branching pattern. This model provides a theoretical basis to study branching as a simple function of the number of branches independently of ordering- and bifurcation-based schemes.

Adaptation, Physiological↗

PubMed2006

Computer-aided design of modular protein devices: Boolean AND gene activation.

Many potentially useful synthetic gene networks require the expression of an engineered gene if and only if two different DNA-binding proteins exist in sufficient concentration. While some natural and engineered systems activate gene expression according to a logical AND-like behavior, they often utilize allosteric or cooperative protein-protein interactions, rendering their components unsuitable for a toolbox of modular parts for use in multiple applications. Here, we develop a quantitative model to demonstrate that a small system of interacting fusion proteins, called a protein device, can activate an engineered gene according to the Boolean AND behavior while using only modular protein domains and DNA sites. The fusion proteins are created from transactivating, DNA-binding, non-DNA binding, and protein-protein interaction domains along with the corresponding peptide ligands. Using a combined kinetic and thermodynamic model, we identify the characteristics of the molecular components and their rates of constitutive production that maximize the fidelity of AND behavior. These AND protein devices facilitate the creation of complex genetic programs and may be used to create gene therapies, biosensors and other biomedical and biotechnological applications that turn on gene expression only when multiple DNA-binding proteins are simultaneously present.

Computer Simulation↗

PubMed1997

The pneumococcal cell wall degrading enzymes: a modular design to create new lysins?

Autolysins are enzymes that degrade different bonds in the peptidoglycan and, eventually, cause the lysis and death of the cell. Streptococcus pneumoniae contains a powerful autolytic enzyme that has been characterized as an N-acetylmuramoyl-L-alanine amidase. We have cloned the lytA gene coding for this amidase and studied in depth the genetics and expression of this gene, which represented the first molecular analysis of a bacterial autolysin. Two observations have been fundamental in revealing further knowledge on the lytic systems of pneumococcus: (a) The well-documented dependence of the pneumococcal autolysin on the presence of choline in the cell wall for activity, and (b) the early observation that most pneumococcal phages also required the presence of this amino-alcohol in the growth medium to achieve a successful liberation of the phage progeny. We concluded that choline would serve as an element of strong selective pressure to preserve certain structures of the host and phage lytic enzymes which should lead to sequence homologies. We constructed active chimeras between the lytic enzymes of S. pneumoniae and its bacteriophages using genes that share sequence homology as well as genes that completely lack homologous regions. In this way, we demonstrated that the pneumococcal lytic enzymes are the result of the fusion of two independent functional modules where the carboxy-terminal domain might be responsible for the specific recognition of choline-containing cell walls whereas the active center of these enzymes should be localized in the N-terminal part of the protein. The modular design postulated for the pneumococcal lysins seems to be a widespread model for many types of microbial proteins and the construction of functional chimeric proteins between the lytic enzymes of pneumococcus and those of several gram-positive microorganisms, like Clostridium acetobutylicum or Lactococcus lactis, provided interesting clues on the modular evolution of proteins. The study of several genes coding for the lytic enzymes of temperate phages of pneumococcus also highlighted on some evolutionary relationships between microorganisms. We suggest that lysogenic relationships may represent a common mechanism by which pathogenic organisms like pneumococcus should undergo a rapid adaptation to an evolving environment.

Bacteriolysis↗

PubMed2004

Two functionally identical modular enhancers in Drosophila troponin T gene establish the correct protein levels in different muscle types.

The control of muscle-specific expression is one of the principal mechanisms by which diversity is generated among muscle types. In an attempt to elucidate the regulatory mechanisms that control fiber diversity in any given muscle, we have focused our attention on the transcriptional regulation of the Drosophila Troponin T gene. Two, nonredundant, functionally identical, enhancer-like elements activate Troponin T transcription independently in all major muscles of the embryo and larvae as well as in adult somatic and visceral muscles. Here, we propose that the differential but concerted interaction of these two elements underlies the mechanism by which a particular muscle-type establish the correct levels of Troponin T expression, adapting these levels to their specific needs. This mechanism is not exclusive to the Troponin T gene, but is also relevant to the muscle-specific Troponin I gene. In conjunction with in vivo transgenic studies, an in silico analysis of the Troponin T enhancer-like sequences revealed that both these elements are organized in a modular manner. Extending this analysis to the Troponin I and Tropomyosin regulatory elements, the two other components of the muscle-regulatory complex, we have discovered a similar modular organization of phylogenetically conserved domains.

Animals↗

PubMed2002

Modular self-assembly of a Y-shaped multiprotein complex from seven nucleoporins.

Now that it is likely that all yeast nucleoporins are known, one of the ultimate goals is the in vitro assembly of the entire nuclear pore complex from its approximately 30 individual components. Here, we report the reconstitution of seven proteins (Nup133p, Nup145p-C, Nup120p, Nup85p, Nup84p, Seh1p and Sec13p) into a heptameric 0.5 MDa nuclear pore subcomplex. We found that double plasmid transformation combined with bi-cistronic mRNA translation allow the expression and assembly of distinct subcomplexes of up to five nucleoporins in a single Escherichia coli cell. During the sequential reconstitution of the Nup84p complex, smaller assembly intermediates can be isolated, which exhibit modular structures determined by electron microscopy that finally make up the whole Y-shaped Nup84p complex. Importantly, a seventh subunit, Nup133p, was incorporated into the complex through its interaction with Nup84p, thereby elongating one arm of the Y-shaped assembly to an approximately 40 nm long stalk. Taken together, our data document that the Nup84p-Nup133p complex self-assembles in a modular concept from distinct smaller nucleoporin construction sets.

Escherichia coli↗

PubMed1995

Modular structural elements in the replication origin region of Tetrahymena rDNA.

Computer analyses of the DNA replication origin region in the amplified rRNA genes of Tetrahymena thermophila identified a potential initiation zone in the 5'NTS [Dobbs, Shaiu and Benbow (1994), Nucleic Acids Res. 22, 2479-2489]. This region consists of a putative DNA unwinding element (DUE) aligned with predicted bent DNA segments, nuclear matrix or scaffold associated region (MAR/SAR) consensus sequences, and other common modular sequence elements previously shown to be clustered in eukaryotic chromosomal origin regions. In this study, two mung bean nuclease-hypersensitive sites in super-coiled plasmid DNA were localized within the major DUE-like element predicted by thermodynamic analyses. Three restriction fragments of the 5'NTS region predicted to contain bent DNA segments exhibited anomalous migration characteristic of bent DNA during electrophoresis on polyacrylamide gels. Restriction fragments containing the 5'NTS region bound Tetrahymena nuclear matrices in an in vitro binding assay, consistent with an association of the replication origin region with the nuclear matrix in vivo. The direct demonstration in a protozoan origin region of elements previously identified in Drosophila, chick and mammalian origin regions suggests that clusters of modular structural elements may be a conserved feature of eukaryotic chromosomal origins of replication.

Animals↗

PubMed1999

Srp2, an SR protein family member of fission yeast: in vivo characterization of its modular domains.

We isolated srp2, a gene encoding a protein composed of two RNA binding domains (RBDs) at the N-terminus followed by an arginine-rich region that is flanked by two short SR (serine/arginine) elements. The RBDs contain the signatures RDADDA and SWQDLKD found in RBD1 and RBD2 of all typical metazoan SR proteins. srp2 is essential for growth. We have analyzed in vivo the role of the modular domains of Srp2 by testing specific mutations in a conditional strain for complementation. We found that RBD2 is essential for function and determines the specificity of RBD1 in Srp2. Replacement of the first RBD with RBD1 of Srp1 of fission yeast does not change this specificity. The two SR elements in the C-terminus of Srp2 are also essential for function in vivo. Cellular distribution analysis with green fluorescence protein fused to portions of Srp2 revealed that the SR elements are necessary to target Srp2 to the nucleus. Furthermore, overexpression of modular domains of Srp2 and Srp1 show different effects on pre-mRNA splicing activity of the tfIId gene. Taken together, these findings are consistent with the notion that the RBDs of these proteins may be involved in pre-mRNA recognition.

Alleles↗