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At least 1,387 records · Page 77Linked to original sources
PubMed1998

On the modularity of recognition memory for object form and spatial location: a topographic ERP analysis.

Event-related potentials from 61 scalp sites were used to examine the brain processes subserving recognition memory for object forms and spatial locations. Subjects memorized line drawings of highly familiar objects and their spatial locations within a two-dimensional matrix. Prior to the test phases a cue indicated whether object-based or spatially-based recognition judgements were required. Recognition judgements were faster and more accurate for spatially-based than for object-based judgements. A variety of topographical differences in the ERP waveforms as a function of recognition task emerged: First, when the cue indicated that object-based judgements were required, negative slow wave activity extending for several hundred ms with a maximum at frontal recording sites was obtained. Conversely when spatially-based judgements were required, slow wave activity developed over parieto-occipital areas. Second, early portions of the old/new effects evoked by the test items (i.e. 300-600 ms after stimulus onset) showed a similar anterior-posterior dissociation as a function of recognition task. Third, for object-based, but not for spatially-based, judgements, late old/new effects (i.e. 700-1600 ms) were found with a clear maximum at right frontal recordings. The results are consistent with the view that functionally and anatomically different brain systems are involved in recognition memory for object form and spatial location. They further suggest that the retrieval of object forms involves conceptual semantic integration processes.

Adult↗
PubMed2004

Modular architecture and novel protein-protein interactions regulating the RGS-containing Rho guanine nucleotide exchange factors.

The regulator of G-protein signaling (RGS)-containing RhoGEFs, including p115RhoGEF, PDZ-RhoGEF, and LARG, represent a novel family of guanine nucleotide exchange factors for RhoA that are regulated by the Galpha(12/13) family of heterotrimeric G proteins. Experimental evidence indicates that the complex architecture of these RhoGEFs provides the structural basis for novel regulatory mechanisms mediated by protein-protein interactions. These include the direct association of their RGS domain with GTP-bound forms of Galpha(12/13) and the binding of the PDZ domain present in PDZ-RhoGEF and LARG to plexins, which are receptors for semaphorins. The carboxyl-terminal region of these GEFs also exerts regulatory properties, including the ability to form dimers, which is inhibitory to their in vivo GEF activity and, in the case of PDZ-RhoGEF, to associate with PAK4, a downstream target of Cdc42. This carboxyl-terminal region also acts as the target for tyrosine kinases, which have a positive effect on the long-term activity of these GEFs. This article describes the experimental strategies that have been utilized to begin unraveling the molecular mechanisms regulating the functional activity of RGS-containing RhoGEFs.

Animals↗
PubMed2002

The modular organization of brain systems. Basal forebrain: the last frontier.

Computational anatomical studies suggest that specific clusters of projection neurons in the basal forebrain together with specific prefrontal and posterior cortical associational regions constitute distributed parts of functional parallel circuits. The predictable sequence of cell clusters consisting of various types of noncholinergic cell populations in the basal forebrain suggests further subdivisions within these circuits. It is possible that similar to the parallel basal ganglia circuits (Alexander and Crutcher, 1990), large number of specialized channels and sub-channels exist within this triangular circuitry that permit parallel, multilevel processing concurrently. The location and size of the active modules may temporarily vary according to the prevalence of state-related diffuse ascending brain stem and specific telencephalic inputs. From this latter group of afferents, the prefrontal input may function as an external threshold control which allocates attentional resources via the basal forebrain to distributed cortical processes in a selective, self-regulatory fashion.

Acetylcholine↗
PubMed2002

Modular recognition of RNA by a human pumilio-homology domain.

Puf proteins are developmental regulators that control mRNA stability and translation by binding sequences in the 3' untranslated regions of their target mRNAs. We have determined the structure of the RNA binding domain of the human Puf protein, Pumilio1, bound to a high-affinity RNA ligand. The RNA binds the concave surface of the molecule, where each of the protein's eight repeats makes contacts with a different RNA base via three amino acid side chains at conserved positions. We have mutated these three side chains in one repeat, thereby altering the sequence specificity of Pumilio1. Thus, the high affinity and specificity of the PUM-HD for RNA is achieved using multiple copies of a simple repeated motif.

Binding Sites↗
PubMed2000

Synthetic spider silk: a modular fiber.

Spiders make their webs and perform a wide range of tasks with up to seven different types of silk fiber. These different fibers allow a comparison of structure with function, because each silk has distinct mechanical properties and is composed of peptide modules that confer those properties. By using genetic engineering to mix the modules in specific proportions, proteins with defined strength and elasticity can be designed, which have many potential medical and engineering uses.

Amino Acid Motifs↗
PubMed1998

Application of artificial neural networks as a non-linear modular modeling technique to describe bacterial growth in chilled food products.

In many chilled, prepared food products, the effects of temperature, pH and %NaCl on microbial activity interact and this should be taken into account. A grey box model for prediction of microbial growth is developed. The time dependence is modeled by a Gompertz model-based, non-linear differential equation. The influence of temperature, pH and %NaCl reflected in the model parameters is described by using low-complexity, black box artificial neural networks (ANN's). The use of this non-linear modeling technique makes it possible to describe more accurately interacting effects of environmental factors when compared with classical predictive microbiology models. When experimental results on the influence of other environmental factors become available, the ANN models can be extended simply by adding more neurons and/or layers.

Bacteria↗
PubMed2001

Modularity in the gain and loss of genes: applications for function prediction.

Genes that are clustered on multiple genomes and are likely to functionally interact tend to be gained or lost together during genome evolution. Here, we demonstrate that exceptions to this pattern indicate relatively distant functional interactions between the encoded proteins. Hence, this can be used to divide predicted clusters of functionally interacting proteins into sub-clusters, and as such, to refine the prediction of their function and functional interactions.

Bacterial Proteins↗
PubMed1997

Modular regulation of muscle gene transcription: a mechanism for muscle cell diversity.

Skeletal, cardiac and smooth muscle cells express overlapping sets of muscle-specific genes, such that some muscle genes are expressed in only a single muscle cell lineages. Recent studies in transgenic mice have revealed that, in many cases, multiple, independent cis-regulatory regions, or modules, are required to direct the complete developmental pattern of expression of individual muscle-specific genes, even within a single muscle cell type. The temporospatial specificity of these myogenic regulatory modules is established by unique combinations of transcription factors and has revealed unanticipated diversity in the regulatory programs that control muscle gene expression. This type of composite regulation of muscle gene expression appears to reflect a general strategy for the control of cell-specific gene expression.

Animals↗
PubMed1998

Standardized structure and modular design of a pharmacokinetic database.

BACKGROUND: The accumulated knowledge on drugs can be used for an individual drug dosage adjustment if it is placed at our disposal in an informatically structured form. THEORY AND METHODS: We have started building up a pharmacokinetic database aimed at adjusting drug dosages, in exemplary form, to patients with renal impairment. Parameters needed for the three dosage adjustment rules (Dettli, Kunin, Holford) and the most general concept of pharmacokinetics constituted the theoretical basis. TWO PROCESSES PERTAIN TO ALL DRUGS: Distribution and elimination. Total drug clearance and at least two parameters representing distribution and elimination processes are closely interdependent in mathematical terms (clearance = volume of distribution*rate of elimination). This relation yields the unifying concept that serves as a prerequisite for a structured recording of 30 assigned pharmacokinetic and pharmacodynamic parameters within an informatic database. SOLUTIONS AND RESULTS: The information is retrieved and referenced from 2383 original publications by means of a standardized input module. The complete database at present contains 15,397 records for 1573 drugs. A programmed meta-analytic algorithm is used to calculate the statistical measures for the central value and variance--as available--from the pooled values of primary records. The statistically standardized parameters are extracted for 6601 pharmacokinetic parameters, and placed at the users disposal with the output module. PRACTICAL UTILITY: Following meta-analysis, published pharmacokinetics can be used as statistical estimates of population parameters. The statistical estimates with variances permit an individual drug dosage adjustment by applying the Bayesian approach or neural networks.

Algorithms↗
PubMed2001

Modular structure of cAMP response element binding protein 2 (CREB2).

The transcription factor cAMP-response element binding protein 2 (CREB2), a member of the family of basic region leucine zipper proteins, has been suggested to function in the brain as a repressor of long-term memory. Using recombinant proteins we show that CREB2 binds in vitro to the palindromic cAMP response element derived from the secretogranin II gene. Recent studies of the chromogranin B, secretogranin II and enkephalin genes showed that CREB2 functioned as a repressor of cAMP-induced transcription. We analyzed the ability of CREB2 to repress transcription using model promoters. A molecular dissection of the CREB2 molecule revealed that CREB2 lacks a transferable repressor domain suggesting that CREB2 may function solely as a "passive" transcriptional repressor. In contrast, "active" repressor domains derived from the thyroid hormone receptor alpha or the NK10 zinc finger protein containing a "Krüppel associated box" could be transfered to a heterologous DNA-binding domain and functioned as fusion proteins in repressing transcription of a reporter gene. In addition, a strong activation domain located at the N-terminus was identified in the CREB2 protein suggesting that CREB2 may act as an activator of transcription by binding to different genetic regulatory elements.

Activating Transcription Factor 4↗