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At least 343 records · Page 19Linked to original sources
PubMed1995

Relationship between frequency and amplitude dependence in the lung: a nonlinear block-structured modeling approach.

During lung constriction, there is an increase in both the frequency and tidal volume (VT) dependences of lung tissue resistance (Rti) and elastance (Eti). This suggests that 1) significant alterations take place in the mechanisms contributing to both the linear and nonlinear characteristics of lung tissues; and 2) the frequency and VT dependences of Rti and Eti are coupled. We examined these issues for the case of sine wave and special pseudorandom inputs by utilizing the theory of nonlinear block-structured systems. Two basic model structures were considered: the Hammerstein and the Wiener structures. The Hammerstein structure is a cascade connection of a nonlinear zero-memory (N) system and a linear dynamic process (L). This structure predicts that frequency and VT dependences of Rti and Eti are decoupled. The Wiener structure is an inverse cascade of these two blocks (i.e., L-N) in which the frequency and VT dependences of Rti and Eti are coupled. These two structures were combined with a nonlinear airway compartment and fitted to measured airway opening and alveolar capsule pressure-flow time domain data in dogs before and after histamine-induced constriction. The best lung model was a linear airway compartment combined with a Wiener structure consisting of a constant-phase linear tissue impedance in cascade with a polynomial nonlinearity, suggesting that frequency and VT dependences of Rti and Eti are indeed coupled during control and constricted conditions. Moreover, histamine caused much larger changes in the linear tissue parameters than in the nonlinear coefficients.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pressure↗
PubMed1980

Secondary structure model for bacterial 16S ribosomal RNA: phylogenetic, enzymatic and chemical evidence.

We have derived a secondary structure model for 16S ribosomal RNA on the basis of comparative sequence analysis, chemical modification studies and nuclease susceptibility data. Nucleotide sequences of the E. coli and B. brevis 16S rRNA chains, and of RNAse T1 oligomer catalogs from 16S rRNAs of over 100 species of eubacteria were used for phylogenetic comparison. Chemical modification of G by glyoxal, A by m-chloroperbenzoic acid and C by bisulfite in naked 16S rRNA, and G by kethoxal in active and inactive 30S ribosomal subunits was taken as an indication of single stranded structure. Further support for the structure was obtained from susceptibility to RNases A and T1. These three approaches are in excellent agreement. The structure contains fifty helical elements organized into four major domains, in which 46 percent of the nucleotides of 16S rRNA are involved in base pairing. Phylogenetic comparison shows that highly conserved sequences are found principally in unpaired regions of the molecule. No knots are created by the structure.

Bacillus↗
PubMed1994

A model structure of the muscle protein complex 4Ca2+.troponin C.troponin I derived from small-angle scattering data: implications for regulation.

We report here a model structure for 4Ca2+.troponin C.troponin I derived from small-angle X-ray and neutron scattering data using a Monte Carlo modeling method. In this model, troponin I appears as a spiral structure that wraps around 4Ca2+.troponin C which adopts an extended dumbbell conformation similar to that observed in the crystal structures of troponin C. The troponin I spiral has the approximate dimensions of an alpha-helix and winds through the hydrophobic "cups" in each globular domain of troponin C. The model is consistent with a body of previously published biochemical data on the interactions between troponin C and troponin I, and suggests the molecular mechanism for the Ca(2+)-sensitive switch that regulates the muscle contraction/relaxation cycle involves a signal transmitted via the central spiral region of troponin I.

Amino Acid Sequence↗
PubMed2004

A mu-class glutathione S-transferase from the marine shrimp Litopenaeus vannamei: molecular cloning and active-site structural modeling.

A cDNA clone coding for a mu-class glutathione S-transferase (GST) was isolated from a hepatopancreas cDNA library from the shrimp Litopenaeus vannamei. The deduced amino acid sequence (215 amino acids) has >50% identity to rodents and other mammals mu-class GSTs. Using RT-PCR, the shrimp GST transcript was detected in hepatopancreas, hemocytes, gills, and muscle, but not in pleopods. The shrimp GST sequence was computer modeled and found to fit the classical two-domain GST structure. Domain I, containing the glutathione (GSH) binding site, is more conserved compared to the flexible C-terminal domain II. Residue Q208 appears to be a key to substrate specificity by comparison with mammalian GST mutants. This position is commonly occupied by serine or threonine in mammalian mu-class GSTs, and shrimp Q208 may affect the affinity to substrates like aminochrome or 1,3-dimethyl-2-cyano-1-nitrosoguanidine. This is the first report of molecular cloning and structural modeling of a crustacean GST and provides new insights into the nature of the detoxification response on marine invertebrates.

Amino Acid Sequence↗
PubMed2002

Development of body image, eating disturbance, and general psychological functioning in adolescent females: a replication using covariance structure modeling in an Australian sample.

OBJECTIVE: The current study is a follow up to a covariance structure modeling (CSM) investigation of predictors of body image, eating dysfunction, and general psychological functioning in U.S. adolescent females. METHOD: Four hundred and seventy Australian girls (13-17 years old) completed measures of teasing history, body dissatisfaction, global psychological functioning, dietary restraint, and bulimic behaviors. They were also measured in order to compute body mass index (BMI). CSM techniques were used to analyze the relationships between these latent variables. Two a priori models were tested, one was selected, and post-hoc model-fitting was undertaken. RESULTS: The final model indicated that BMI directly influenced teasing, which directly influenced body dissatisfaction. Body dissatisfaction influenced both global psychological functioning and restriction, whereas restriction had a direct influence on bulimia. Global psychological functioning also had a direct influence on bulimia. DISCUSSION: The results support previous research indicating that teasing and body dissatisfaction are risk factors for the development of eating disturbances.

Adolescent↗
PubMed2002

A simple structured model for biomass and extracellular enzyme production with recombinant Saccharomyces cerevisiae YPB-G.

A simple structured model is proposed for simulating batch cultivation data on growth, substrate utilization, and heterologous enzyme production of recombinant Saccharomyces cerevisiae YPB-G. The enzyme is a fusion protein displaying alpha-amylase and glucoamylase activities. Cell growth is modulated mainly by intracellular substrate and ethanol concentrations. Intracellular substrate concentration is evaluated by means of the extracellular substrate and biomass concentrations. Extracellular alpha-amylase and glucoamylase activities are taken to depend on biomass concentration. The nine parameters of the proposed model are determined using nonlinear estimation techniques, and the model is validated against experiments not used in parameter determination. The model developed simulates glucose consumption, cell mass, alpha-amylase and glucoamylase production in a batch system. Simulation and experimental results are found to be in good agreement.

Biomass↗
PubMed2004

Marginal structural models for analyzing causal effects of time-dependent treatments: an application in perinatal epidemiology.

Marginal structural models (MSMs) are causal models designed to adjust for time-dependent confounding in observational studies of time-varying treatments. MSMs are powerful tools for assessing causality with complicated, longitudinal data sets but have not been widely used by practitioners. The objective of this paper is to illustrate the fitting of an MSM for the causal effect of iron supplement use during pregnancy (time-varying treatment) on odds of anemia at delivery in the presence of time-dependent confounding. Data from pregnant women enrolled in the Iron Supplementation Study (Raleigh, North Carolina, 1997-1999) were used. The authors highlight complexities of MSMs and key issues epidemiologists should recognize before and while undertaking an analysis with these methods and show how such methods can be readily interpreted in existing software packages, including SAS and Stata. The authors emphasize that if a data set with rich information on confounders is available, MSMs can be used straightforwardly to make robust inferences about causal effects of time-dependent treatments/exposures in epidemiologic research.

Adult↗
PubMed1985

Stage-structure models of populations with distinct growth and development processes.

We extend the repertoire of stage-structure models which can be described in terms of delay-differential equations, by analysing models where the processes of growth and development within a stage are distinct. This permits the use of delay-differential equation models in situations where both population numbers and total biomass are dynamically significant.

Aging↗
PubMed2006

A simple track structure model of ion beam radiotherapy.

A simple radiotherapy ion beam calculation based on the cellular track structure model, using in vitro cell survival parameters fitted from recent experimental data, is presented. The calculation represents a single-fraction ion exposure (roughly corresponding to a 2 Gy fraction of megavolt X rays) and exploits concepts used in clinical radiotherapy, such as entrance, or 'skin' ion dose. The depth distribution of cells surviving their irradiation by a beam of 385 MeV amu(-1) carbon ions is calculated over the range of the stopping ions, as a sequence of track-segments, in the continuous slowing-down approximation. An interpretation of the 'clinical relative biological effectiveness' concept is suggested.

Animals↗
PubMed2006

Structural model of an antistasin/notch-like fusion protein from the cocoon wall of the aquatic leech, Theromyzon tessulatum.

The aquatic leech, Theromyzon tessulatum, secretes a proteinaceous cocoon with extraordinary physical properties (e.g., proteolytic, thermal resiliency). The deduced amino acid sequence of a major protein (Tcp-Theromyzon cocoon protein) from the T. tessulatum cocoon wall has been used to model the endogenous structure of the Tcp protein. The Tcp protein sequence comprises six internal repeats, each containing 12 ordered Cys residues. Amino acid alignments suggest that the region Cys1-->6 is homologous to antistasin, a leech anticoagulant, and Cys7-->12 is homologous to an epidermal growth factor-like domain found in notch-class proteins, which play critical roles in development, signaling, and adhesion throughout the Animalia. Modeling of individual domains (i.e., antistasin and notch) positions multiple hydrophobic and charged residues on the surface. When the antistasin and notch domains were fused, hydrophobic pockets appeared that may facilitate a polymerization mechanism. Collectively, the predicted features of our Tcp model are consistent with the physical properties of the leech cocoon wall.

Animals↗
PubMed2004

A secondary structural model of the 28S rRNA expansion segments D2 and D3 from rootworms and related leaf beetles (Coleoptera: Chrysomelidae; Galerucinae).

We analysed the secondary structure of two expansion segments (D2, D3) of the 28S rRNA gene from 229 leaf beetles (Coleoptera: Chrysomelidae), the majority of which are in the subfamily Galerucinae. The sequences were compared in a multiple sequence alignment, with secondary structure inferred primarily from the compensatory base changes in the conserved helices of the rRNA molecules. This comparative approach yielded thirty helices comprised of base pairs with positional covariation. Based on these leaf beetle sequences, we report an annotated secondary structural model for the D2 and D3 expansion segments that will prove useful in assigning positional nucleotide homology for phylogeny reconstruction in these and closely related beetle taxa. This predicted structure, consisting of seven major compound helices, is mostly consistent with previously proposed models for the D2 and D3 expansion segments in insects. Despite a lack of conservation in the primary structure of these regions of insect 28S rRNA, the evolution of the secondary structure of these seven major motifs may be informative above the nucleotide level for higher-order phylogeny reconstruction of major insect lineages.

Animals↗
PubMed1997

Pretreatment status variables and treatment implementation for cocaine misuse: a latent variable structural model pilot study.

This study was designed to test the utility of a latent variable structural equation covariance model for cocaine misuser treatment outcome research. Three structural models were tested for goodness-of-fit of data obtained from a sample of subjects (N = 206) receiving drug misuser treatment in four treatment settings in a treatment program in Nevada. Fourteen variables were entered into the structural equations. An adequately fitting model was found (CFK = .956), [chi 2(6, N = 205) = 15.77, p > .01]. The subjects' discharge rates did not differ significantly by the severity of cocaine misuse at admission.

Adolescent↗
PubMed2000

Succinyl-CoA:3-ketoacid CoA transferase (SCOT): cloning of the human SCOT gene, tertiary structural modeling of the human SCOT monomer, and characterization of three pathogenic mutations.

The activity of succinyl-CoA:3-ketoacid CoA transferase (SCOT; locus symbol OXCT; EC 2.8.3.5) is the main determinant of the ketolytic capacity of tissues. Hereditary SCOT deficiency causes episodic ketoacidosis. Here we describe the human SCOT gene, which spans more than 100 kb and contains 17 exons, on chromosome 5p13. We report pathogenic missense mutations in three SCOT-deficient patients designated GS04, 05, and 06. GS04 is a G219E/G324E compound; GS05 is a V221M homozygote, and GS06 is a G324E homozygote. We constructed a tertiary structural model of human SCOT by homology modeling based on the known structure of Acidaminococcus fermentans glutaconate CoA transferase. The model predicts that V221 and G219 are on the dimerizing surface, whereas G324 is near the active site. SCOT activity was reduced to a comparable degree in all three patients, but in a transient expression assay in SCOT-deficient fibroblasts, cDNAs containing G219E and G324E produced no detectable activity, whereas V221M constructs yielded approximately 10% of the control peptide level and detectable specific activity. Interestingly, GS05 had the mildest clinical course reported to date and detectable levels of SCOT protein in fibroblasts.

Acidosis↗
PubMed2006

Dissecting the mechanism of Epac activation via hydrogen-deuterium exchange FT-IR and structural modeling.

Exchange proteins directly activated by cAMP (Epac) make up a family of cAMP binding domain-containing proteins that play important roles in mediating the effects of cAMP through the activation of downstream small GTPases, Ras-proximate proteins. To delineate the mechanism of Epac activation, we probed the conformation and structural dynamics of Epac using amide hydrogen-deuterium (H-D) exchange coupled with Fourier transform infrared spectroscopy (FT-IR) and structural modeling. Our studies show that unlike that of cAMP-dependent protein kinase (PKA), the classic intracellular cAMP receptor, binding of cAMP to Epac does not induce significant changes in overall secondary structure and structural dynamics, as measured by FT-IR and the rate of H-D exchange, respectively. These results suggest that Epac activation does not involve significant changes in the amount of exposed surface areas as in the case of PKA activation, and conformational changes induced by cAMP in Epac are most likely confined to small local regions. Homology modeling and comparative structural analyses of the CBDs of Epac and PKA lead us to propose a model of Epac activation. On the basis of our model, Epac activation by cAMP employs the same underlying structural principal utilized by PKA, although the detailed structural and conformational changes associated with Epac and PKA activation are significantly different. In addition, we predict that during Epac activation the first beta-strand of the switchboard switches its conformation to a alpha-helix, which folds back to the beta-barrel core of the CBD and interacts directly with cAMP to form the base of the cAMP-binding pocket.

Amino Acid Sequence↗
PubMed2005

A new beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) from Helicobacter pylori: Molecular cloning, enzymatic characterization, and structural modeling.

Helicobacter pylori is a gram-negative pathogenic bacterium that causes peptic ulcer disease and gastric cancer, and studies of the related potent enzymes associated with this bacterium are urgent for the discovery of novel drug targets. In bacteria, beta-hydroxyacyl-acyl carrier protein (ACP) dehydratase (FabZ) is a potent enzyme in fatty acid biosynthesis and catalyzes the dehydration of beta-hydroxyacyl-ACP to trans-2-acyl-ACP. In this study, the cloning and enzymatic characterization of FabZ from H. pylori strain SS1 (HpFabZ) were reported, and the gene sequence of HpfabZ was deposited in the GenBank database. Enzyme dynamic analysis showed that HpFabZ had a K(m) of 82.6+/-4.3 microM toward its substrate analog crotonoyl-CoA. Dynamic light scattering and native-PAGE investigations suggested that HpFabZ exists as hexamer in native state. Enzymatic characterization and thermal-induced unfolding analysis based on circular dichroism spectral measurements indicated that HpFabZ is very stable against high temperature (90 degrees C). Such a high stability of HpFabZ was well elucidated by the strong H-bonds and hydrophobic interactions among the HpFabZ hexamer as investigated in the modeled HpFabZ hexamer structure. Our current study is hoped to provide useful information in better understanding the FabZ of H. pylori strain and further supply possible hints in the discovery of anti-bacterial compounds using HpFabZ as target.

Amino Acid Sequence↗
PubMed2004

Modeling structurally variable regions in homologous proteins with rosetta.

A major limitation of current comparative modeling methods is the accuracy with which regions that are structurally divergent from homologues of known structure can be modeled. Because structural differences between homologous proteins are responsible for variations in protein function and specificity, the ability to model these differences has important functional consequences. Although existing methods can provide reasonably accurate models of short loop regions, modeling longer structurally divergent regions is an unsolved problem. Here we describe a method based on the de novo structure prediction algorithm, Rosetta, for predicting conformations of structurally divergent regions in comparative models. Initial conformations for short segments are selected from the protein structure database, whereas longer segments are built up by using three- and nine-residue fragments drawn from the database and combined by using the Rosetta algorithm. A gap closure term in the potential in combination with modified Newton's method for gradient descent minimization is used to ensure continuity of the peptide backbone. Conformations of variable regions are refined in the context of a fixed template structure using Monte Carlo minimization together with rapid repacking of side-chains to iteratively optimize backbone torsion angles and side-chain rotamers. For short loops, mean accuracies of 0.69, 1.45, and 3.62 A are obtained for 4, 8, and 12 residue loops, respectively. In addition, the method can provide reasonable models of conformations of longer protein segments: predicted conformations of 3A root-mean-square deviation or better were obtained for 5 of 10 examples of segments ranging from 13 to 34 residues. In combination with a sequence alignment algorithm, this method generates complete, ungapped models of protein structures, including regions both similar to and divergent from a homologous structure. This combined method was used to make predictions for 28 protein domains in the Critical Assessment of Protein Structure 4 (CASP 4) and 59 domains in CASP 5, where the method ranked highly among comparative modeling and fold recognition methods. Model accuracy in these blind predictions is dominated by alignment quality, but in the context of accurate alignments, long protein segments can be accurately modeled. Notably, the method correctly predicted the local structure of a 39-residue insertion into a TIM barrel in CASP 5 target T0186.

Algorithms↗
PubMed2005

Structural model of the amyloid fibril formed by beta(2)-microglobulin #21-31 fragment based on vibrational spectroscopy.

A structural model of amyloid fibril formed by the #21-31 fragment of beta2-microglobulin is proposed from microscope IR measurements on specifically 13C-labeled peptide fibrils and Raman spectra of the dispersed fibril solution. The 13C-shifted amide frequency indicated the secondary structure of the labeled residues. The IR spectra have demonstrated that the region between F22 and V27 forms the core part with the extended beta-sheet structure. Raman spectra indicated the formation of a dimer with a disulfide bridge between C25 residues.

Amino Acid Sequence↗