SEARCH · PubMed Health

Results for “Partially Identified Models”

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 505 records · Page 28Linked to original sources

PubMed2001

The 3' end of hepatitis E virus (HEV) genome binds specifically to the viral RNA-dependent RNA polymerase (RdRp).

Hepatitis E virus (HEV) is the major cause of acute epidemic and sporadic hepatitis in the developing world. It is a positive-strand RNA virus with a genome length of about 7.2 kb. The replication mechanism of this virus is virtually unexplored. Identification of the regulatory elements involved in initiation of replication may help in designing specific inhibitors for therapy. In the positive-stranded RNA viruses the initiation of replication requires interaction of the 3' end of genome with its RNA-dependent RNA polymerase (RdRp) and possibly host-derived cofactors for synthesis of the minus-strand replicative intermediate. Secondary structure prediction of the conserved 3' end of the infectious HEV genome was carried out to identify possible stem-loop structures necessary for RNA-protein interaction and the model was confirmed by structure probing experiments. Electrophoretic mobility-shift assays showed specific binding of purified and refolded recombinant HEV RdRp protein to the 3' end of its RNA genome containing the poly(A) stretch. Mutations at the 3' end, in which the stem-loop structures were partially or completely destroyed or recreated revealed that the two stem-loop structures SL1 and SL2 at the 3' end and the poly(A) stretch are necessary for this binding. The interacting nucleotides in such an interaction were further identified by generating footprints of the complex by Pb(II)-induced hydrolysis. This specific binding of viral RdRp to the 3' end of HEV RNA directs the synthesis of complementary-strand RNA and thus such a binding domain might assume the role of a possible cis-acting element as a potential site for the initiation of replication.

3' Untranslated Regions↗

PubMed2026

Research on multi-trait genome association study method based on Shannon information entropy.

BACKGROUND: Genetic analysis of complex traits is crucial for elucidating disease mechanisms and biological inheritance processes. However, traditional Genome-wide Association Study (GWAS) for single trait often fail to capture the synergistic effects of genetic loci on multiple traits. METHODS: This study proposes a method for analyzing the association between multiple traits and gene regions based on Shannon information entropy. Innovatively, Shannon information entropy is introduced to integrate gene region information as genetic entropy, thereby constructing an Inverse Shannon Entropy-Multi-Trait Association Analysis of Gene Region genetic model (InvSE-MTAGR). Furthermore, a partial regression test is applied to the model to establish the Inverse Partial Shannon Entropy-Multi-Trait Association Analysis of Gene Region method (InvPSE-MTAGR). When performing multi-trait analysis with InvSE-MTAGR, the method achieved statistical significance by accumulating minor effects, thereby enhancing the ability to identify pleiotropic gene regions. RESULTS: The simulation results showed that the proposed multi-trait gene region association analysis method performed well in terms of both Type I error rate control and statistical power. Leveraging tomato and sorghum datasets for validation, the proposed multi-trait gene region association analysis method based on Shannon information entropy accurately pinpointed most of the gene regions harboring candidate genes. CONCLUSION: The study reveals the advantage of multi-trait method in integrating weak-effect pleiotropic signals and capturing the correlation among traits, which provides an efficient theoretical tool for dynamic analysis of complex multi-trait genetic networks and multi-target collaborative breeding of crops.

Genome-Wide Association Study↗

PubMed1997

Naloxone activation of mu-opioid receptors mutated at a histidine residue lining the opioid binding cavity.

The mu-opioid receptor is the principal site of action in the brain by which morphine, other opiate drugs of abuse, and endogenous opioid peptides effect analgesia and alter mood. A member of the seven-transmembrane domain (TM) G protein-coupled receptor (GPCR) superfamily, the mu-opioid receptor modulates ion channels and second messenger effectors in an opioid agonist-dependent fashion that is reversible by the classic opiate antagonist naloxone. Mutation of a histidine residue (His297) in TM 6 afforded agonist-like G protein-coupled signal transduction mediated by naloxone and other alkaloid antagonists and enhanced the intrinsic activity of documented alkaloid partial agonists, including buprenorphine. The intrinsic activities of all opioid peptide agonists and antagonists tested were not altered at the His297 mutant receptors. Consistent with a role for the TM 6 histidine in maintaining high affinity binding sites for opioid agonists and antagonists, opioid ligand-dependent protection of this residue from a histidine-specific alkylating agent indicated that the His297 side chain is positioned in or very near the binding cavity. The TM 6 His297 mutants identify a discrete region of the receptor critical for determining whether a specific drug pharmacophore triggers receptor activation. Because many GPCRs possess a similarly positioned TM histidine residue, our findings with the mu-opioid receptor may extend to these receptors and potentially serve as a model for rational design of therapeutic GPCR partial agonists and antagonists.

Alkaloids↗

PubMed1992

Changes in milk pH and bicarbonate during 20 days of lactation in the guinea pig.

Milk samples were obtained from lactating albino guinea pigs after 4 to 6 h of separation from their offspring. The samples were collected in 5-ml glass vials and capped immediately. They were transported rapidly to a pH-gas analyzer for measurements of pH, bicarbonate, base excess, and partial pressure of CO2. Eight guinea pigs were sampled daily for 20 d for a total of 160 observations. Analysis of variance indicated animal and day differences. Regression analyses over days revealed equations of best fit to be quadratic, although stepwise trends were observed in the data as well. The quadratic model for pH was Y(pH) = 6.996 - .057X + .002X2, where X was day of lactation (R2 = .54). The model for bicarbonate was Y (-HCO3 in milliequivalents per liter) = 8.896 - .659X + .0202X2 (R2 = .60). For base excess, the model was Y (in milliequivalents per liter) = -22.65 - 1.99X + .069X2 (R2 = .58). The model for partial pressure of CO2 was Y (millimeters of Hg) = 38.63 + 1.06X - .080X2 (R2 = .33). Decreases in pH and bicarbonate were parallel to changes in mammary epithelial cells of guinea pigs in which degeneration of mechanisms responsible for two important ingredients relating to milk volume occur. These have been identified previously as reductions in lactose and potassium. Synthesis of the enzyme carbonic anhydrase with its resultant bicarbonate production may be related in some way to these components of milk secretion.

Acid-Base Equilibrium↗

PubMed1997

Dimer model for the microfibrillar protein fibulin-2 and identification of the connecting disulfide bridge.

Fibulin-2 is a novel extracellular matrix protein frequently found in close association with microfibrils containing either fibronectin or fibrillin. The entire protein and its predicted domains were obtained as recombinant products and examined by ultracentrifugation and electron microscopy. This demonstrated a disulfide-linked homodimer of 175 kDa subunits. Partial reduction to monomers identified specifically an odd Cys574 residue responsible for dimer formation in one of three anaphylatoxin-like modules that constitute the central globular domain I (13 kDa) of fibulin-2. Furthermore, a Cys574-Ser mutation abolished disulfide connection but not non-covalent dimerization of fibulin-2. The C-terminal region (85 kDa) was shown to represent a 35-nm-long rod consisting of 11 calcium-binding EGF-like modules (domain II) and a small terminal globe (domain III). The unique N-terminal domain N (55 kDa) was also rod-shaped (approximately 38 nm) and rich in galactosamine indicating extensive O-glycosylation. A dimer model is proposed indicating mainly a rod-like shape of 80 nm length based on an anti-parallel association of two subunits through their domains I. This model also implies alignment of domains II and N between different subunits. This was demonstrated by surface plasmon resonance assay which showed a distinct interaction between domains N and II with a Kd of approximately 0.7 microM.

Amino Acid Sequence↗

PubMed2006

Computational prediction of solubilizers' effect on partitioning.

A computational model for the prediction of solubilizers' effect on drug partitioning has been developed. Membrane/water partitioning was evaluated by means of immobilized artificial membrane (IAM) chromatography. Four solubilizers were used to alter the partitioning in the IAM column. Two types of molecular descriptors were calculated: 2D descriptors using the MOE software and 3D descriptors using the Volsurf software. Structure-property relationships between each of the two types of descriptors and partitioning were established using partial least squares, projection to latent structures (PLS) statistics. Statistically significant relationships between the molecular descriptors and the IAM data were identified. Based on the 2D descriptors structure-property relationships R(2)Y=0. 99 and Q(2)=0.82-0.83 were obtained for some of the solubilizers. The most important descriptor was related to logP. For the Volsurf 3D descriptors models with R(2)Y=0.53-0.64 and Q(2)=0.40-0.54 were obtained using five descriptors. The present study showed that it is possible to predict partitioning of substances in an artificial phospholipid membrane, with or without the use of solubilizers.

Chromatography↗

PubMed1998

Early assessment of motor dysfunctions aids in successful occlusion of the middle cerebral artery.

Occlusion of the rodent middle cerebral artery by embolism, using an intraluminal filament, produces behavioral alterations which resemble many symptoms associated with stroke. This model has been used to examine treatment interventions for the disease, however, variable success rate in completely blocking the middle cerebral artery may present inconclusive interpretation of the data. To detect successful occlusion of the middle cerebral artery, we demonstrate here sensitive and reliable behavioral parameters including the elevated body swing test, the postural tail-hang test, the spontaneous rotational test, and the forelimb akinesia test. These assays provide a criterion for identifying animals with incomplete occlusion which could promote host-related spontaneous recovery and might confound true effects of experimental therapies on ischemia-induced dysfunctions. From a practical standpoint, the early reliable identification of partial cerebral ischemia aids in immediate and efficient adjustments of the surgical procedure to create a complete and stable ischemia stroke animal model.

Animals↗

PubMed2005

Genetically based resistance to the antiinflammatory effects of methotrexate in the air-pouch model of acute inflammation.

OBJECTIVE: Low-dose methotrexate (MTX), a mainstay in the treatment of rheumatoid arthritis, is effective in only 60-70% of patients, a finding mirrored by poor antiinflammatory efficacy in some animal models, most notably collagen-induced arthritis. To determine whether genetic factors or the model itself is responsible for the poor response to MTX, we directly compared the responses of 4 inbred mouse strains to MTX in the air-pouch model of acute inflammation. METHODS: The exudate leukocyte count and adenosine concentration were determined in inbred mice treated with MTX (0.75 mg/kg intraperitoneally every week for 4 weeks) or vehicle 4 hours after injection of carrageenan into the air pouch using previously described methods. Quantitative trait locus mapping was performed using an in silico, or computer-based, method to identify loci potentially associated with each phenotype. RESULTS: MTX significantly reduced the exudate leukocyte count in C57BL/6J and BALB/cJ mice, but not DBA/1J (the strain used in the collagen-induced arthritis model) or DBA/2J mice. In a parallel manner, MTX increased adenosine concentration in inflammatory exudates of C57BL/6J and BALB/cJ mice, but not DBA/1J or DBA/2J mice. Antiinflammatory and adenosine responses to MTX in DBA/1J x C57BL/6J F(1) and F(2) offspring were most consistent with single genetic loci being responsible for each phenotype. In silico mapping identified partially overlapping loci containing candidate genes involved in both responses. CONCLUSION: Genetic factors contribute to the antiinflammatory efficacy of MTX, and a single locus involved in MTX-induced adenosine up-regulation is likely responsible for the observed resistance to MTX in DBA/1J mice.

Acute Disease↗

PubMed1999

Structure of personality disorders from the perspective of the Revised Neo Personality Inventory domain scales and the Psychopathology-5 Scales.

This study tested the generality and comprehensiveness of the five-factor model of personality as applied to the Personality Adjective Checklist's (Strack, 1987) personality disorder scales. A sample of 258 undergraduates (113 men and 145 women) completed the Personality Adjective Checklist, the Revised NEO Personality Inventory, and the Psychopathology-5 Scales for partial course credit. A combined principal axis analysis with varimax rotation was performed for nonoverlapping scales of the Personality Adjective Checklist, the Revised NEO Personality Inventory domain scales and the Psychopathology-5 scales. The results indicated four factors which were identified as Neuroticism, Extraversion, Disagreebleness, and Conscientiousness. Openness did not emerge as a separate factor. These results supported the comprehensiveness but not the generality of the five-factor model as applied to personality disorders.

Adult↗

PubMed1995

Numerical modeling of the cornea's lamellar structure and birefringence properties.

A model of the cornea's lamellar structure is proposed that is capable of explaining experimental results obtained for the transmission of normal-incidence polarized light through rabbit and bovine cornea. The model consists of a large number of planar lamellae, each approximated as a uniaxial birefringent layer, stacked one upon another with various angular orientations. Polarized light transmission through the composite system is modeled theoretically by use of the Jones matrix formalism. The light transmission is calculated numerically for a large number of model lamellae arrangements, each generated from a statistical description, and histograms are constructed of various properties of the light transmission, including the minimum and maximum cross-polarized output intensities. It is demonstrated that various structural and optical parameters of the lamellae arrangements of actual corneas may be estimated by comparison of the calculations with detailed experimental data. Certain characteristics of the histograms are identified that permit a clear distinction between random and partially ordered systems. Comparisons with previously published experimental data provide strong evidence that the lamellae orientations are not entirely random, but rather a significant fraction are oriented in a fixed, preferred direction.

Animals↗

PubMed2002

De novo prediction of three-dimensional structures for major protein families.

We use the Rosetta de novo structure prediction method to produce three-dimensional structure models for all Pfam-A sequence families with average length under 150 residues and no link to any protein of known structure. To estimate the reliability of the predictions, the method was calibrated on 131 proteins of known structure. For approximately 60% of the proteins one of the top five models was correctly predicted for 50 or more residues, and for approximately 35%, the correct SCOP superfamily was identified in a structure-based search of the Protein Data Bank using one of the models. This performance is consistent with results from the fourth critical assessment of structure prediction (CASP4). Correct and incorrect predictions could be partially distinguished using a confidence function based on a combination of simulation convergence, protein length and the similarity of a given structure prediction to known protein structures. While the limited accuracy and reliability of the method precludes definitive conclusions, the Pfam models provide the only tertiary structure information available for the 12% of publicly available sequences represented by these large protein families.

Calibration↗

PubMed1994

Error-tolerant identification of peptides in sequence databases by peptide sequence tags.

We demonstrate a new approach to the identification of mass spectrometrically fragmented peptides. A fragmentation spectrum usually contains a short, easily identifiable series of sequence ions, which yields a partial sequence. This partial sequence divides the peptide into three parts-regions 1, 2, and 3-characterized by the added mass m1 of region 1, the partial sequence of region 2, and the added mass m3 of region 3. We call the construct, m1 partial sequence m3, a "peptide sequence tag" and show that it is a highly specific identifier of the peptide. An algorithm developed here that uses the sequence tag to find the peptide in a sequence database is up to 1 million-fold more discriminating than the partial sequence information alone. Peptides can be identified even in the presence of an unknown posttranslational modification or an amino acid substitution between an entry in the sequence database and the measured peptide. These concepts are demonstrated with model and practical examples of electrospray mass spectrometry/mass spectrometry of tryptic peptides. Just two to three amino acid residues derived by fragmentation are enough to identify these peptides. In peptide mapping applications, even less information is necessary.

Algorithms↗

PubMed2002

Reactivity, secondary structure, and molecular topology of the Escherichia coli sulfite reductase flavodoxin-like domain.

The flavodoxin-like domain, missing in the three-dimensional structure of the monomeric, simplified model of the Escherichia coli sulfite reductase flavoprotein component (SiR-FP), has now been expressed independently. This 168 amino acid protein was named SiR-FP18 with respect to its native molecular weight and represents the FMN-binding domain of SiR-FP. This simplified biological object has kept the main characteristics of its counterpart in the native protein. It could incorporate FMN exclusively and stabilize a neutral air-stable semiquinone radical. Both the radical and the fully reduced forms of SiR-FP18 were able to transfer their electrons to DCPIP or cytochrome c quantitatively. SiR-FP18 was able to form a highly stable complex with SiR-HP, the hemoprotein component of the sulfite reductase containing an iron-sulfur cluster coupled to a siroheme. In agreement with the postulated catalytic cycle of SiR-FP, only the fully reduced form of SiR-FP18 could transfer one electron to SiR-HP, the transferred electron being localized exclusively on the heme. As isolated SiR-FP18 has kept the main characteristics of the FMN-binding domain of the native protein, a structural analysis by NMR was performed in order to complete the partial structure obtained previously. Structural modeling was performed using sequence homologues, cytochrome P450 reductase (CPR; 29% identity) and bacterial cytochrome P450 (P450-BM3; 26% identity), as conformational templates. These sequences were anchored using common secondary structural elements identified from heteronuclear NMR data measured on the protein backbone. The resulting structural model was validated, and subsequently refined using residual (C(alpha)-C', N-H(N), and C'-H(N)) dipolar couplings measured in an anisotropic medium. The overall fold of SiR-FP18 is very similar to that of bacterial flavodoxins and of the flavodoxin-like domain in CPR or P450-BM3.

Amino Acid Sequence↗

PubMed2005

Usefulness of near-infrared reflectance (NIR) spectroscopy and chemometrics to discriminate fishmeal batches made with different fish species.

Near-infrared reflectance (NIR) spectroscopy combined with chemometrics was used to identify and authenticate fishmeal batches made with different fish species. Samples from a commercial fishmeal factory (n = 60) were scanned in the NIR region (1100-2500 nm) in a monochromator instrument in reflectance. Principal component analysis (PCA), dummy partial least-squares regression (DPLS), and linear discriminant analysis (LDA) based on PCA scores were used to identify the origin of fishmeal produced using different fish species. Cross-validation was used as validation method when classification models were developed. DPLS correctly classified 80 and 82% of the fishmeal samples. LDA calibration models correctly classified >80% of fishmeal samples according to fish species The results demonstrated the usefulness of NIR spectra combined with chemometrics as an objective and rapid method for the authentication and identification of fish species used to manufacture the fishmeal.

Animals↗

PubMed1996

A psychophysiological investigation of the selection and the use of partial stimulus information in response choice.

Two alternative explanations were examined for why selective response activation sometimes starts before stimulus identification is complete (e.g., J. O. Miller & S. A. Hackley, 1992) and sometimes starts only after stimulus identification is complete (e.g., R. De Jong, M. Wierda, G. Mulder, & L. J. M. Mulder, 1988). Distinct psychophysiological methods related to stimulus identification and response selection provided evidence suggesting that partial stimulus information is identified but is or is not used before the stimulus is identified more fully, depending on task requirements. This result (a) suggests strategic adaptation of task performance, (b) is inconsistent with particular discrete and continuous models of information processing, and (c) shows the existence of a central selection mechanism that can prevent the automatic activation of responses associated with preliminary available stimulus information.

Adult↗

PubMed2004

Expression and characterization of the protein Rv1399c from Mycobacterium tuberculosis. A novel carboxyl esterase structurally related to the HSL family.

The Mycobacterium tuberculosis genome contains an unusually high number of proteins involved in the metabolism of lipids belonging to the Lip family, including various nonlipolytic and lipolytic hydrolases. Driven by a structural genomic approach, we have biochemically characterized the Rv1399c gene product, LipH, previously annotated as a putative lipase. Rv1399c was overexpressed in E. coli as inclusion bodies and refolded. Rv1399c efficiently hydrolyzes soluble triacylglycerols and vinyl esters. It is inactive against emulsified substrate and its catalytic activity is strongly inhibited by the diethyl paranitrophenyl phosphate (E600). These kinetic behaviors unambiguously classify Rv1399c as a nonlipolytic rather than a lipolytic hydrolase. Sequence alignment reveals that this enzyme belongs to the alpha/beta hydrolase fold family and shares 30-40% amino acid sequence identity with members of the hormone-sensitive lipase subfamily. A model of Rv1399c derived from homologous three-dimensional structures reveals a canonical catalytic triad (Ser162, His290 and Asp260) located at the bottom of a solvent accessible pocket lined by neutral or charged residues. Based on this model, kinetic data of the Arg213Ala mutant partially explain the role of the guanidinium moiety, located close to His290, to confer an unusual low pH shift of the catalytic histidine in the wild type enzyme. Overall, these data identify Rv1399c as a new nonlipolytic hydrolase from M. tuberculosis and we thus propose to reannotate its gene product as NLH-H.

Amino Acid Sequence↗

PubMed2006

Does coronary vasodilation after adenosine override endothelin-1-induced coronary vasoconstriction?

Endothelin-1 is a powerful coronary vasoconstrictor that is overexpressed in coronary artery disease. Adenosine is a powerful coronary vasodilator used for myocardial perfusion imaging to identify flow-limiting coronary artery stenosis. Therefore, in an animal model we tested the hypothesis that intracoronary endothelin-1 may cause myocardial perfusion abnormalities by positron emission tomography (PET) at resting conditions that may persist or only partially improve after intravenous adenosine stress in the absence of myocardial scar and flow-limiting stenosis. Fourteen dogs underwent serial PET perfusion imaging with rubidium-82 before and after subselective intracoronary infusion of endothelin-1, followed by intravenous and then intracoronary adenosine. Small physiological doses of endothelin-1 infused into the mid-left circumflex coronary artery caused quantitatively significant resting perfusion abnormalities that normalized after intracoronary adenosine but not consistently after intravenous adenosine used for diagnostic imaging. After effects of adenosine abated, resting perfusion defects returned, lasting up to 5 h in some animals. Cumulative doses of endothelin-1 caused perfusion defects that did not normalize after intravenous adenosine. In an animal model without myocardial scar or flow-limiting stenosis, intracoronary endothelin-1 causes visually apparent, quantitatively significant, long-lasting myocardial perfusion defects at resting conditions that may persist or only partially improve after intravenous adenosine used for diagnostic imaging. These results may potentially explain resting perfusion abnormalities or heterogeneity by clinical PET that may persist or only partially improve after adenosine stress perfusion imaging in the absence of myocardial scar and flow-limiting stenosis.

Adenosine↗

PubMed2004

Histidine-proline rich glycoprotein (HPRG) binds and transduces anti-angiogenic signals through cell surface tropomyosin on endothelial cells.

The anti-angiogenic properties of the histidine-proline-rich (H/P) domain of HPRG have recently been described (Juarez JC, et al. Cancer Research 2002; 62: 5344-50). However, the binding site that mediates these properties is unknown. HPRG is evolutionarily, functionally and structurally related to cleaved high molecular weight kininogen (HKa), an anti-angiogenic polypeptide that stimulates apoptosis of proliferating endothelial cells through binding to cell-surface tropomyosin (Zhang J-C, et al. Proc Natl Acad Sci USA 2002; 99: 12224-9). In this study, we demonstrate that HPRG binds with high affinity to FGF-2-stimulated human umbilical vein endothelial cells (HUVEC) and immobilized tropomyosin in a Zn2+ or pH-dependent manner, and that this interaction is mediated by the H/P domain of HPRG. At least two binding sites for HPRG, tropomyosin and heparan sulfate proteoglycans (HSPs), were identified on the surface of FGF-2-activated endothelial cells. Translocation of tropomyosin to the surface of HUVEC occurred in response to FGF-2, and the anti-angiogenic activity of HPRG in a Matrigel plug model was partially inhibited by soluble tropomyosin. These results suggest that HPRG binds to endothelial cell surface tropomyosin which at least partially mediates the antiangiogenic effects of HPRG.

Angiogenesis Inhibitors↗