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Results for “Functional potential”

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PubMed2002

Expression of CD154 on renal cell carcinomas and effect on cell proliferation, motility and platelet-activating factor synthesis.

CD40 activation by CD154 may trigger diverse cellular responses, ranging from proliferation and differentiation to growth suppression and cell death, in normal and malignant cells. However, the pathophysiologic role of CD154 expressed by tumor cells remains unclear. We have investigated the expression of the CD40-CD154 system in 24 primary cultures derived from renal cell carcinomas, its correlation with tumor stage and its potential functional significance. We found coexpression of CD40 and CD154 in most of the renal carcinoma cell lines. CD154, but not CD40 expression, significantly correlated with tumor stage. Moreover, renal carcinoma cell lines also released the soluble form of CD154 into the supernatant. CD40 engagement by CD154 did not affect apoptosis or survival. On the contrary, CD154 stimulated cell proliferation, motility and production of PAF, a phospholipid mediator of inflammation with angiogenic properties. Furthermore, the renal carcinoma cell lines expressed PAF-R. Blockade of PAF-R by WEB-2170, a PAF-R antagonist, abolished the CD154-dependent motility, indicating a role for PAF synthesized after CD154 stimulation in renal carcinoma cell motility. In conclusion, this study identifies new functional properties for CD154, which are potentially relevant for the growth and dissemination of renal carcinoma cells.

Apoptosis↗

PubMed2001

Exploring protein sequence space using knowledge-based potentials.

Knowledge-based potentials can be used to decide whether an amino acid sequence is likely to fold into a prescribed native protein structure. We use this idea to survey the sequence-structure relations in protein space. In particular, we test the following two propositions which were found to be important for efficient evolution: the sequences folding into a particular native fold form extensive neutral networks that percolate through sequence space. The neutral networks of any two native folds approach each other to within a few point mutations. Computer simulations using two very different potential functions, M. Sippl's PROSA pair potential and a neural network based potential, are used to verify these claims.

Amino Acid Sequence↗

PubMed2005

Bovine BMP osteoinductive potential enhanced by functionalized dextran-derived hydrogels.

This study evaluated functionalized dextran-derived hydrogels as BMP carriers using both in vitro and in vivo models. In vitro release kinetics indicated that dextran-derived hydrogels could retain rhBMP-2 growth factor in a variable manner depending on their functionalization ratio. The potential of these hydrogels when combined with extracted bovine BMP to enhance the bone formation was evaluated in a rat ectopic model. The largest osteoinduction was found when using hydrogels exhibiting the highest growth factor retention capacity. In addition, some implanted hydrogels demonstrated a capacity to induce an in-vivo calcification certainly related to their chemical composition. These properties make these materials interesting osteoconductive BMP carriers, allowing to decrease the amount of implanted factor required for bone regeneration.

Animals↗

PubMed2006

Prediction of hydrogen hydrate equilibrium by integrating ab initio calculations with statistical thermodynamics.

This paper addresses a new calculation approach for the prediction of hydrogen hydrate equilibrium by introducing the concept of a single hydrogen cluster in one cavity. By integrating ab initio calculations with classical statistical thermodynamics, this approach enables the van der Waals model to predict the dissociation pressure of hydrogen hydrates. Compared to hydrates formed by light hydrocarbon gases, structure II (sII) hydrogen hydrates stably encage two and four hydrogen molecules in the small and large cavities, respectively. By treating two hydrogen molecules or four hydrogen molecules as one rigid body cluster, we determine ab initio binding energies between water molecules and hydrogen clusters at the MP2 level with the 6-31++G(2d,2p) basis set. These binding energies will be used to determine the parameters of the Exp-6 potential function from which the smooth cell potential and the Langmuir constant of each cluster are calculated. Then, the dissociation pressure is determined using the Zele-Lee-Holder cell distortion model: 105, 625, and 2000 bar at 150, 200, and 250 K, respectively.

Journal Article↗

PubMed2003

Genomic organization and comparative sequence analysis of the mouse and human FRS2, FRS3 genes.

The signaling adapter proteins FRS2 and FRS3 are implicated in the transmission of extracellular signals from nerve growth factor (NGF) or fibroblast growth factor (FGF) receptors to the Ras/mitogen-activated protein kinase signaling cascade. This study presents the genomic sequence and exon-intron organization of the mouse FRS2 and FRS3 loci as well as their evolutionary conservation with their human counterparts. Both FRS2 and FRS3 contain 5 coding exons spanning over 7 kb of genomic sequence with similar exon sizes and organization. Comparative genomic sequence analyses show a highly conserved genomic organization between mouse and human in both FRS2 and FRS3 genes. Non-coding sequences, highly conserved between mouse and human, were identified in the FRS3 introns that may potentially function as regulatory elements. To assay potential differences in their patterns of expression, RT-PCR analysis was used to assay FRS2 and FRS3 expression in the developing embryo and neural tube (NT) during the time of neurogenesis.

Adaptor Proteins, Signal Transducing↗

PubMed2004

A path integral influence functional for excess electron in fluids: Density-functional formulation.

In this paper, we propose a path integral influence functional from a solvent to determine a self-correlation function of a quantum particle in classical simple fluid. It is shown that the influence functional is related to a grand potential functional of the pure solvent under a three-dimensional external field arising from a classical isomorphic polymer, on which the quantum particle is mapped. The influence functional can be calculated from the self-correlation function, the solute-solvent and the solvent-solvent pair correlation function. The obtained equation of the self-correlation function is applied to an excess electron problem in fluid helium. The Fourier path-integral Monte Carlo method is employed to perform the path integral of the electron. The solute-solvent pair correlation function is estimated from a reference interaction site model integral equation. These results obtained form our proposed influence functional and from that proposed by Chandler, Singh, and Richardson are compared with those provided by a path integral Monte Carlo simulation with the explicit helium solvent.

Journal Article↗

PubMed2006

Measuring changes in functional status among patients with schizophrenia: the link with cognitive impairment.

Cognitive impairment associated with schizophrenia (CIAS) includes neuropsychological deficits in attention, working memory, verbal learning, and problem solving. These deficits have been shown to be linked to impairment in functional status (eg, social behavior, work performance, and activities of daily living) among patients with schizophrenia in cross-sectional studies. Less is known about the relationship between cognitive and functional change over time, such as potential functional implications of treatment-related improvement in CIAS. The purpose of this review is to summarize research on the association between change in CIAS and change in functional status, to discuss responsiveness of functional outcomes measures, and to provide recommendations for future research and measure development. Nine longitudinal studies were located on the link between CIAS and functional status, and 8 functional outcomes measures were used across these studies. The 9 studies offer initial support for a link between change in cognitive function and change in functional status. However, inconsistent findings across studies indicate that available research is preliminary, and substantial questions remain unanswered. Shortcomings of functional status measures are noted: most instruments were not developed for the target population, and none have demonstrated responsiveness to cognitive change among schizophrenic patients. It is recommended that new functional outcome measures be developed that are specifically designed to be responsive to change in cognition, with domains previously shown to be related to cognitive ability. When creating new functional outcomes measures for assessment of patients with schizophrenia, responsiveness to change in CIAS should be evaluated as part of the development and validation process.

Activities of Daily Living↗

PubMed1999

Heme oxygenase: who needs it?

Heme is a molecule that is synthesized by the sequential actions of eight enzymes and is ubiquitous throughout nature. For many years it has been known that heme is also catabolized to yield biliverdin (which is subsequently reduced to bilirubin), one atom of iron, and one molecule of carbon monoxide. There has been a recent explosion of interest in this degradative process that is catalyzed by the rate-limiting enzyme, heme oxygenase. In particular, there has been a special interest in the potential physiological and pathological roles that may be played by these breakdown products. This minireview will examine some of these potential functional correlates, with special emphasis on potential oxidant and antioxidant effects of the bilirubin, carbon monoxide, and iron that result from the activity of heme oxygenase.

Animals↗

PubMed2006

Optimized effective potential from a correlated wave function: optimized effective potential-generalized valence bond (OEP-GVB).

The optimized effective potential (OEP) method allows orbital-dependent functionals to be used in density functional theory. Traditionally the orbital-dependent functional of interest has been the Hartree-Fock energy, leading to exact exchange density functional theory. Here we present results that use a generalized valence-bond (GVB) wave function, a multiconfigurational wave function that includes static correlation and dissociates to the proper limits. We demonstrate the effectiveness of the OEP-GVB method by showing the dissociation of H2 and the excitation spectrum of He.

Journal Article↗

PubMed2003

Using a neural network and spatial clustering to predict the location of active sites in enzymes.

Structural genomics projects aim to provide a sharp increase in the number of structures of functionally unannotated, and largely unstudied, proteins. Algorithms and tools capable of deriving information about the nature, and location, of functional sites within a structure are increasingly useful therefore. Here, a neural network is trained to identify the catalytic residues found in enzymes, based on an analysis of the structure and sequence. The neural network output, and spatial clustering of the highly scoring residues are then used to predict the location of the active site.A comparison of the performance of differently trained neural networks is presented that shows how information from sequence and structure come together to improve the prediction accuracy of the network. Spatial clustering of the network results provides a reliable way of finding likely active sites. In over 69% of the test cases the active site is correctly predicted, and a further 25% are partially correctly predicted. The failures are generally due to the poor quality of the automatically generated sequence alignments. We also present predictions identifying the active site, and potential functional residues in five recently solved enzyme structures, not used in developing the method. The method correctly identifies the putative active site in each case. In most cases the likely functional residues are identified correctly, as well as some potentially novel functional groups.

Algorithms↗

PubMed2002

A protein folding potential that places the native states of a large number of proteins near a local minimum.

BACKGROUND: We present a simple method to train a potential function for the protein folding problem which, even though trained using a small number of proteins, is able to place a significantly large number of native conformations near a local minimum. The training relies on generating decoys by energy minimization of the native conformations using the current potential and using a physically meaningful objective function (derivative of energy with respect to torsion angles at the native conformation) during the quadratic programming to place the native conformation near a local minimum. RESULTS: We also compare the performance of three different types of energy functions and find that while the pairwise energy function is trainable, a solvation energy function by itself is untrainable if decoys are generated by minimizing the current potential starting at the native conformation. The best results are obtained when a pairwise interaction energy function is used with solvation energy function. CONCLUSIONS: We are able to train a potential function using six proteins which places a total of 42 native conformations within approximately 4 A rmsd and 71 native conformations within approximately 6 A rmsd of a local minimum out of a total of 91 proteins. Furthermore, the threading test using the same 91 proteins ranks 89 native conformations to be first and the other two as second.

Models, Molecular↗

PubMed1993

Novel interactions between dermal dendrocytes and mast cells in human skin. Implications for hemostasis and matrix repair.

BACKGROUND: Dermal dendrocytes are a newly-recognized cell type in human skin. They express coagulation Factor XIIIa (FXIIIa), also known as fibrin stabilizing factor, and their number is increased in certain inflammatory dermatoses. Current dogma suggests that these recently described cells may represent a subset of antigen-presenting macrophages. The present study therefore was undertaken to examine further the phenotype and potential function of these novel cells. EXPERIMENTAL DESIGN: Conventional ultrastructure, single and dual label immunofluorescence and immunocytochemistry, confocal laser scanning microscopy, and immunoelectron microscopy were used to define structure and potential heterogeneity among dermal dendrocytes. Human neonatal foreskin organ culture exposed to mast cell secretagogues, inhibitors, and relevant recombinant cytokines (tumor necrosis factors alpha) was employed to gain insight into functional characteristics of FXIIIa expression. RESULTS: We found that dermal dendrocytes are phenotypically unique dermal cells, separate from conventional macrophages, with antigenic heterogeneity of FXIIIa and CD34 expression related to their microanatomical location in the dermis. Moreover, they express specialized membrane-matrix plaques that may stabilize their placement in various dermal strata. Finally, superficial subpopulations of dermal dendrocytes are closely-associated with mast cells and show enhanced FXIIIa expression in response to mast cell degranulation, an event that appears to result from liberation of mast cell tumor necrosis factor in the dendrocyte microenvironment. CONCLUSIONS: These new insights establish dermal dendrocytes as distinctive fixed skin cells with potential functional capacity for mast cell-dependent facilitation of fibrin cross-linking and matrix remodeling. These previously unrecognized phenotypic and functional characteristics of dermal dendrocytes therefore may be relevant to cellular interactions responsible for cutaneous wound healing and hemostasis.

Cell Communication↗

PubMed2005

Accelerating quantum mechanical/molecular mechanical sampling using pure molecular mechanical potential as an importance function: the case of effective fragment potential.

Acceleration of sampling from a quantum mechanical/effective fragment mechanical (QM/EFP) potential is explored with effective fragment potential (EFP) as an importance function. EFP, generated on the fly, is found to be an excellent choice for an importance function for a QM/EFP potential. This technique is used to find nine stationary points of a blocked amino acid with twelve waters in a semi-automated way.

Journal Article↗

PubMed2005

Cryopreservation of canine ovaries by vitrification.

The cryopreservation of ovarian tissues is a technology with significant potential for the preservation of the genetic resource materials of working dogs, including guide dogs for the blind. However, no attempt has been reported on cryopreservation of the canine ovary. Thus, we evaluated a vitrification method for cryopreservation of canine ovaries and determined the potential functionality of vitrified-warmed canine ovaries by means of transplantation into non-obese diabetic-severe combined immunodeficiency (NOD-SCID) mice. All ovarian tissues cryopreserved by vitrification were morphologically normal in terms of histology. Cryopreserved ovaries were transplanted into the ovarian bursa of the NOD-SCID mice, and the xenografts were recovered from 23 of 23 mice (100%) 4 weeks after the operation. The transplanted canine tissue was tightly adhered to the mouse ovary. Although antral follicle formation did not occur after grafting, proliferating cell nuclear antigen immunoreactivity was detectable in many of the granulosa cells in the primary follicles of the grafts. These results indicate that cryopreservation of the canine ovary by vitrification appears to have the potential to restore endocrine function and ovulation potential.

Animals↗

PubMed2006

Genetic variation and the mitogen-activated protein kinase (MAPK) signaling pathway.

Non-synonymous single nucleotide polymorphisms (nsSNPs) are known to alter protein function, contributing to disease susceptibility. This report explores the nature of nsSNPs in the gene products of the highly conserved mitogen-activated protein kinase (MAPK) signaling pathways already implicated in cancer development. MAPK signaling pathways regulate cellular processes such as proliferation, differentiation, apoptosis, and survival mediated through interconnected signaling cascades. Using the dbSNP database, we have identified 25 nsSNPs in 17 out of 98 MAPK genes studied. Computational algorithms were used to predict whether the amino acid substitutions were evolutionarily tolerated, or affected putative functional units such as phosphorylation sites, protein motifs and domains. This study predicts that 36% of nsSNPs are likely to have functional consequences, based on evolutionary conservation analysis, and 36% based on phosphorylation prediction analysis. All such nsSNPs represent potentially functional and disease-causing/modifying alleles. More interestingly, the epistatic relationships discussed in this report represent potential synergistic/ antagonistic/additive effects of nsSNP combinations found within the same protein, or within members of the same protein complex and cascades. This strategy can effectively determine which nsSNPs potentially alter protein function, and can be utilized to study the genetic architecture and disease association of other biological protein complexes and networks.

Algorithms↗

PubMed1985

Management of the fetus with congenital hydronephrosis II: Prognostic criteria and selection for treatment.

Selecting appropriate management for the fetus with bilateral congenital hydronephrosis depends on our ability to accurately assess the severity of existing renal damage and to predict the potential for recovery of renal and pulmonary function if the obstruction is relieved. We reviewed our experience with 20 fetuses with congenital bilateral hydronephrosis to determine the prognostic value of various criteria used to assess functional potential, including temporary catheter exteriorization to measure fetal urine output and composition. Based on autopsy, biopsy, or clinical outcome, ten fetuses were classified retrospectively as "poor function," and ten fetuses as "good function." The good function group could be distinguished from the poor function group by the following criteria: Amniotic fluid (AF) status at presentation (P less than .001), ultrasound appearance of the fetal kidneys (P less than .05), fetal urine sodium and chloride concentration and osmolarity (P less than .001), and hourly urine output (P less than .02), but not by fetal urine iothalamate excretion or potassium and creatinine concentrations (P greater than .05). Based on these results, we have identified prognostic criteria that accurately identify the fetus with "good function" from the fetus with "poor function." We also reviewed the clinical management of our last 12 unreported cases. Ten fetuses had undergone diagnostic catheter placement and in utero renal function testing. This led to placement of a therapeutic indwelling catheter-shunt in seven fetuses (three required multiple shunts) and a suprapubic vesicostomy in another. Catheter related complications, including three cases of chorioamnionitis, emphasize the need for better methods of in utero decompression in selected cases. Our ability to select appropriate management has improved markedly.

Biopsy↗

PubMed2006

Revisiting the hexane-water interface via molecular dynamics simulations using nonadditive alkane-water potentials.

We present results addressing properties of a polarizable force field for hexane based on the fluctuating charge (FQ) formalism and developed in conjunction with the Chemistry at Harvard Molecular Mechanics (CHARMM) potential function. Properties of bulk neat hexane, its liquid-vapor interface, and its interface with a polarizable water model (TIP4P-FQ) are discussed. The FQ model is compared to a recently modified alkane model, C27r, also based on the CHARMM potential energy function. With respect to bulk properties, both models predict bulk density within 1%; the FQ model predicts the liquid vaporization enthalpy within 2%, while the C27r force field underestimates the property by roughly 20% (and in this sense reflects the quality of the C27r force field across the spectrum of linear and branched alkanes). The FQ hexane model realistically captures the dielectric properties of the bulk in terms of a dielectric constant of 1.94, in excellent agreement with experimental values in the range of 1.9-2.02. This behavior is also in conformity with a recent polarizable alkane model based on Drude oscillators. Furthermore, the bulk dielectric is essentially captured in the infinite frequency, or optical, dielectric contribution. The FQ model is in this respect a more realistic force field for modeling lipid bilayer interiors for which most current state-of-the-art force fields do not accurately capture the dielectric environment. The molecular polarizability of the FQ model is 11.79 A3, in good agreement with the range of experimental and ab initio values. In contrast to FQ models of polar solvents such as alcohols and water, there was no need to scale gas-phase polarizabilities in order to avoid polarization catastrophes in the pure bulk. In terms of the liquid-vapor and liquid-liquid interfaces, the FQ model displays a rich orientational structure of alkane and water in the respective interfacial systems, in general conforming with earlier simulation studies of such interfaces. The FQ force field shows a marked deviation in the interfacial dipole potentials computed from the charge densities averaged over simulation trajectories. At the liquid-vapor interface, the FQ model predicts a potential drop of -178.71 mV in contrast to the C27r estimate of -433.80 mV. For the hexane-water interface, the FQ force field predicts a dipole potential drop of -379.40 mV in contrast to the C27r value of -105.42 mV. Although the surface dipole potential predicted by the FQ model is roughly 3.5 times that predicted by the C27r potential, it is consistent with reported experimental potentials across solvated lipid bilayers in the range of 400-600 mV.

Alkanes↗

PubMed1999

Placenta growth factor: potential role in pregnancy.

PROBLEM: In spite of the known requirement for adequate vascularity during placentation, little is known regarding the regulation of angiogenic growth factor production by trophoblast. Placenta growth factor (PIGF) is a recently discovered angiogenic growth factor whose expression is relatively limited to trophoblast. METHOD OF STUDY: Current literature of PIGF was reviewed, with emphasis on its expression, regulation, role in angiogenesis, and potential function(s) at the maternal-fetal interface. RESULTS: PIGF is abundantly expressed by trophoblast, which implies that it could act in a paracrine manner to modulate vascular development, stability, and/or function within the decidua and placental villi. In addition, expression of the PIGF receptor, fms-like tyrosine kinase (flt-1) receptor, on trophoblast raises the potential for an autocrine role of PIGF in regulating trophoblast growth and/or function. CONCLUSIONS: The potential for PIGF to influence both vascular endothelial cells and trophoblast suggests that aberrant trophoblast production of PIGF could compromise cellular function during gestation and contribute to the vascular and placental pathologies noted in many obstetric complications.

Female↗